Federal Grant Award Summary

The National Institute on Drug Abuse (NIDA) awarded the University of Nebraska Medical Center (UNMC) a Project Grant totaling $544,256 under the Drug Use and Addiction Research Programs (CFDA 93.279) to investigate the role of microglial ferritinophagy in HIV and cocaine-mediated neuroinflammation. The research project, initiated May 15, 2026 and concluding February 28, 2031, addresses the persistent neuroinflammation and cognitive decline experienced by approximately 30-60% of people living with HIV despite effective antiretroviral therapy. The project will examine how HIV transactivator of transcription (TAT) protein, antiretroviral medications, and cocaine exposure cooperatively disrupt lysosomal function and iron homeostasis in microglia—the brain's resident immune cells—and will evaluate C381, a novel brain-penetrant lysosomal activator, as a potential therapeutic intervention to restore cellular function and reduce neuroinflammation.

The research deliverables encompass fundamental mechanistic studies of ferritinophagy disruption in microglial cells and translational development of therapeutic strategies targeting iron-mediated oxidative stress and neuroinflammation in people living with HIV who have comorbid stimulant use disorder. The project advances NIDA's programmatic priorities in basic and translational neuroscience research addressing substance use, addiction-related comorbidities, and HIV/AIDS through investigation of novel molecular pathways and identification of candidate compounds for clinical development.